PROPOSAL FOR A COMPUTATIONAL MODEL TO STUDY THE SELECTIVITY BETWEEN PTP1B AND ITS ALLOSTERIC INHIBITORS
Diabetes mellitus type II has spread as a problematic pandemia for countries all over the world. Despite of the current available treatments, approved drugs still show undesirable side effects, loss of efficacy or they target symptoms instead of causes. Since its discovery, protein tyrosine phosphatase 1B has emerged as a very promising target against this disease. Despite of the information about the enzyme, there is no knowledge regarding the selectivity between this enzyme and its closest homologue, lymphocyte T tyrosine phosphatase, responsible of complicate side effects. In this study different computational approaches have let us to highlight the importance of a phenylalanine residue located in protein tyrosine phosphatase 1B, but no in its homologue, as a crucial hotspot that causes selectivity. These results let to explain the observed selectivity and they can be used as a guide for the design of new inhibitors.